Development of novel in-vitro chemical tools to simulate gastro-intestinal and lung environments in order to evaluate bioaccessibility of contaminants

儿童经常通过多种途径接触有毒物质，如多环芳烃（PAH）和金属，包括摄入污染的土壤和吸入空气中的颗粒物（PM）。在对受污染场地进行的风险评估研究中，假设摄入或吸入材料中的有毒物质100%进入血液（生物可利用性）可能导致不切实际的高风险估计。相反，使用吸入或摄入的污染物中可溶于模拟胃肠道条件或模拟肺液（生物可及性）的部分，通过具有成本效益的体外试验测量，可以帮助环境工程师和风险评估人员获得更准确的风险估计。同时，这种化学方法需要减少使用动物试验，这涉及到强烈的道德，技术和财务问题。尽管最近的进展，在化学生物利用度的研究应用于金属污染的土壤，许多工作需要推进的科学基础，将多环芳烃生物可及性测试到污染的特定网站的风险评估。我的研究计划的目标是开发新的和改进的体外工具，用于口腔生物可及性评估（摄入和吸入）的金属和多环芳烃污染的土壤，空气中的颗粒物和儿童消费品。更确切地说，我的工作将旨在调查和挑战最近开发的多环芳烃体外生物可及性测试（FOREShT和IVG），并在评估合成脂质汇对体外化学生物利用度的影响结果使用广泛的工业多环芳烃污染的土壤。在PAH污染场地的情况下，这项研究计划的成功将允许减少土地清理成本，制定更准确的特定场地复垦标准。此外，这项研究计划带来的前景，实施侵入性较低，更可持续的补救办法。这项创新的研究计划还旨在获得有关使用Gamble溶液和人工溶酶体液模拟肺液中与空气中PM相关的多环芳烃和金属的生物可及性的知识。最后，基于我们最近在玩具和低成本珠宝中金属的化学生物利用度方面的开创性工作，该研究计划还将专注于开发急需的IVG生物可及性测试的动态版本，以模拟长期暴露于摄入的物品。总的来说，该计划将使高素质的环境工程师（1 PDF，3博士，2硕士，6本科生）的培训，谁将能够推进知识和开发严格的体外测试，深入了解这些工具将（和应该）由环境工程师和科学家在现场修复和风险评估的范围内使用。

Children are regularly exposed to toxic substances such as polycyclic aromatic hydrocarbons (PAHs) and metals via multiple pathways, including contaminated soil ingestion and inhalation of airborne particulate matter (PM). In risk assessment studies conducted on contaminated sites, assuming that 100% of a toxic substance in ingested or inhaled material enters the bloodstream (bioavailable) may lead to unrealistically high risk estimates. On the contrary, using the fraction of an inhaled or ingested pollutant which is soluble in simulated gastrointestinal conditions or simulated lung fluids (bioaccessible), measured via cost effective in-vitro tests, can help environmental engineers and risk assessors to obtain more accurate risk estimates. Such a chemical approach entails, at the same time, a reduction in the use of animal testing which involves strong ethical, technical, and financial issues. In spite of recent progress in chemical bioavailability research applied to metal-contaminated soils, much work is needed to advance the scientific basis for incorporating PAH bioaccessibility testing into contaminated site-specific risk assessments. The objective of my research program is to develop novel and improved in-vitro tools for oral bioaccessibility assessment (ingestion and inhalation) of metals and PAHs in contaminated soils, airborne particulate matter and children’s consumer products. More precisely, my work will aim at investigating and challenging recently developed PAH in-vitro bioaccessibility tests (FOREShT and IVG) and at assessing the influence of synthetic lipid sinks on in-vitro chemical bioavailability results using a wide array of industrial PAH-contaminated soils. In the case of PAH-contaminated sites, the success of this research program will allow for reduced land clean-up costs, following the formulation of more accurate site-specific reclamation criteria. Moreover, this research program brings the prospect of implementing less intrusive and more sustainable remediation approaches. This innovative research program also aims at gaining knowledge on  bioaccessibility in simulated lung fluids of PAHs and metals associated with airborne PMs using Gamble’s solution and artificial lysosomal fluids. Finally, building on our recent and pioneer work on chemical bioavailability of metals in toys and low-cost jewelry, this research program will also focus on developing a much-needed, dynamic version of the IVG bioaccessibility test, to simulate prolonged exposure to ingested items. Overall, this program will enable the training of highly qualified environmental engineers (1 PDF, 3 PhD, 2 MSc, 6 undergraduates) who will able to advance knowledge and develop rigorous in-vitro tests, with a deep understanding of how these tools will (and should) be used by environmental engineers and scientists within the scope of site remediation and risk assessment.